P1517: HUMORAL AND CELLULAR IMMUNE RESPONSES TO SARS-COV-2 NATURAL INFECTION OR VACCINATION IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): A STUDY BY ERIC, THE EUROPEAN RESEARCH INITIATIVE ON CLL
Authors: Alessandro Campanella, Antonella Capasso, Caterina Taccetti, Silvia Heltai, Elisa Albi, Yair Herishanu, Sabine Haggenburg, Thomas Chatzikonstantinou, Michael Doubek, Magdalena Kättström, Krzysztof Giannopoulos, Martin Simkovic, Carol Moreno, Massimo Massaia, Horia Bumbea, Salem Al Shimmari, Pamela Ranghetti, Eleonora Perotta, Francesca Martini, Emanuela Sant’antonio, Maria Colia, Catalina Combi, Shai Levi, Arnon Kater, Mette Hazenberg, Inger Nijhof, Quincy Hofsink, Christos Demosthenous, Jana Kotaskova, Joanna Zaleska, Filip Vrbacky, Alba Mora, Davide Bisogno, Ignazio Ezio Tripoli, Viola Maria Popov, Viviana Roman, Eloise Scarano, Michela Frenquelli, Lydia Scarfò, Kostas Stamatopoulos, Paolo Ghia
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: The profound immune dysregulation of patients (pts) with chronic lymphocytic leukemia (CLL) put them at risk of severe COVID19. Previous studies showed that seroconversion rate after SARS-Cov-2 vaccine in pts with CLL was lower than in the healthy population, in particular in those on active treatment. Little is known about cellular-mediated immune responses and the effect of targeted therapies upon infection and vaccination. Aims: We aimed at investigating the humoral and cellular immunogenicity of SARS-CoV-2 in pts with CLL after vaccination or natural infection and understanding the impact of targeted therapies. Methods: Spike protein antibodies (Abs) were measured in sera collected 2-4 weeks after the first two doses of mRNA vaccine (399 pts) and 2-8 weeks after the first booster dose (95 pts). We analyzed and compared the humoral and cellular response in a cohort of pts with CLL after the second booster dose (29 pts) and in those 4-16 weeks after SARS-CoV-2 infection (71 pts). In these patients, we evaluated by flow cytometry the presence of spike-specific T cells by means of a multiparametric analysis. Patients were further analyzed based on their treatment status and type. Results: SARS-CoV-2 infection induced detectable Abs (>0.4 U/ml) at frequencies not significantly different among all patients categories stratified by treatment status. Seroconversion rates were: 63% (15/24) in untreated/off treatment (NT) pts, 68% (28/41) in pts on BTKi, and 100% (6/6) in pts on venetoclax (VEN). Notably, the antibody titer was lower in the BTKi group with a median Abs concentration of 150 U/ml (range 4-2500) compared to 2500 U/ml (8-2500) in NT pts and 799 U/ml (105-2500) in VEN pts (Table 1). Seroconversion rates of NT and VEN pts after the first two doses were not significantly different from those measured after natural infection but with lower Abs titer. Seroconversion occurred in 60% of NT (128/212) with a median of 38 U/ml (0.5-2500) and in 64% of VEN (7/11) pts with a median of 27 U/ml (1.1-2500). This is at variance with the seroconversion rate of vaccinated BTKi pts: after the first two doses, 27% (47/176) seroconverted with a median of 19 U/ml (0.75-2500). Abs titer increased along with the number of booster doses administered, though, even after the second booster dose, the seroconversion rate in the BTKi group was only 36% (8/22) with a median Abs concentration of 74 U/ml (2-2500) (Table 1). At variance, T cell responses in the post-infection setting were present in all pts regardless of treatment status with at least one marker of spike-specific activation. NT pts (n=21) showed only a trend toward a qualitatively better T cell response than BTKi pts (n=34), more frequently expressing multiple activation markers on CD4+ T cells (52% in NT vs 32% in BTKi) and at least one marker on CD8+ T cells (86% in NT vs 62% in BTKi). Interestingly, we documented cellular responses in the vast majority of vaccinated pts on BTKi (18/21, 86%) and only 3/21 (14%) did not show spike-specific T cell responses (Table 1). Summary/Conclusion: Our data show that pts with CLL are able to generate SARS-CoV-2 specific cellular immunity without appreciable differences between natural infection and vaccination, though qualitatively lower under BTKi treatment. Similarly, humoral responses after natural SARS-CoV-2 infection are not impacted by the concurrent anti-leukemic treatment while, as previously shown, pts on BTKi show lower seroconversion rate and lower Abs titers upon vaccination. This reassures on the efficacy of vaccination in pts with CLL, being able to elicit a universal T cell response.Keywords: B-CLL, COVID-19